Materials patterned with high-aspect-ratio nanostructures have features on similar length scales to cellular components. These surfaces are an extreme topography on the cellular level and have become useful tools for perturbing and sensing the cellular environment. Motivation comes from the ability of high-aspect-ratio nanostructures to deliver cargoes into cells and tissues, access the intracellular environment, and control cell behavior. These structures directly perturb cells' ability to sense and respond to external forces, influencing cell fate, and enabling new mechanistic studies. Through careful design of their nanoscale structure, these systems act as biological metamaterials, eliciting unusual biological responses. While predominantly used to interface eukaryotic cells, there is growing interest in nonanimal and prokaryotic cell interfacing. Both experimental and theoretical studies have attempted to develop a mechanistic understanding for the observed behaviors, predominantly focusing on the cell-nanostructure interface. This review considers how high-aspect-ratio nanostructured surfaces are used to both stimulate and sense biological systems.

/pdf/high-aspect-ratio-nanostructured-surfaces-as-biological-4lbi856znm.pdf

High-Aspect-Ratio Nanostructured Surfaces as Biological Metamaterials

Surface topography profoundly influences cell adhesion, differentiation, and stem cell fate control. Numerous studies using a variety of materials demonstrate that nanoscale topographies change the intracellular organization of actin cytoskeleton and therefore a broad range of cellular dynamics in live cells. However, the underlying molecular mechanism is not well understood, leaving why actin cytoskeleton responds to topographical features unexplained and therefore preventing researchers from predicting optimal topographic features for desired cell behavior. Here we demonstrate that topography-induced membrane curvature plays a crucial role in modulating intracellular actin organization. By inducing precisely controlled membrane curvatures using engineered vertical nanostructures as topographies, we find that actin fibers form at the sites of nanostructures in a curvature-dependent manner with an upper limit for the diameter of curvature at ∼400 nm. Nanotopography-induced actin fibers are branched actin nucleated by the Arp2/3 complex and are mediated by a curvature-sensing protein FBP17. Our study reveals that the formation of nanotopography-induced actin fibers drastically reduces the amount of stress fibers and mature focal adhesions to result in the reorganization of actin cytoskeleton in the entire cell. These findings establish the membrane curvature as a key linkage between surface topography and topography-induced cell signaling and behavior.

https://www.pnas.org/content/pnas/116/46/23143.full.pdf

Membrane curvature underlies actin reorganization in response to nanoscale surface topography

Engineering the drug carrier biointerface to overcome biological barriers to drug delivery

Layered double hydroxides (LDHs) are an emergent class of biocompatible inorganic lamellar nanomaterials that have attracted significant research interest owing to their high surface-to-volume ratio, the capability to accumulate specific molecules, and the timely release to targets. Their unique properties have been employed for applications in organic catalysis, photocatalysis, sensors, drug delivery, and cell biology. Given the widespread contemporary interest in these topics, time-to-time it urges to review the recent progresses. This review aims to summarize the most recent cutting-edge reports appearing in the last years. It firstly focuses on the application of LDHs as catalysts in relevant chemical reactions and as photocatalysts for organic molecule degradation, water splitting reaction, CO2 conversion, and reduction. Subsequently, the emerging role of these materials in biological applications is discussed, specifically focusing on their use as biosensors, DNA, RNA, and drug delivery, finally elucidating their suitability as contrast agents and for cellular differentiation. Concluding remarks and future prospects deal with future applications of LDHs, encouraging researches in better understanding the fundamental mechanisms involved in catalytic and photocatalytic processes, and the molecular pathways that are activated by the interaction of LDHs with cells in terms of both uptake mechanisms and nanotoxicology effects.

Layered Double Hydroxides: A Toolbox for Chemistry and Biology

Topography of the extracellular environment is now recognized as a major biophysical regulator of cell behavior and function. The study of the influence of patterned substrates on cells, named contact guidance, has greatly benefited from the development of micro and nano-fabrication techniques, allowing the emergence of increasingly diverse and elaborate engineered platforms. The purpose of this review is to provide a comprehensive view of the process of contact guidance from cellular to subcellular scales. We first classify and illustrate the large diversity of topographies reported in the literature by focusing on generic cellular responses to diverse topographical cues. Subsequently, and in a complementary fashion, we adopt the opposite approach and highlight cell type-specific responses to classically used topographies (arrays of pillars or grooves). Finally, we discuss recent advances on the key subcellular and molecular players involved in topographical sensing. Throughout the review, we focus particularly on neuronal cells, whose unique morphology and behavior have inspired a large body of studies in the field of topographical sensing and revealed fascinating cellular mechanisms. We conclude by using the current understanding of the cell-topography interactions at different scales as a springboard for identifying future challenges in the field of contact guidance.

/pdf/cellular-and-subcellular-contact-guidance-on-microfabricated-bk5ldivdf1.pdf

Cellular and Subcellular Contact Guidance on Microfabricated Substrates.

Biomaterial substrates can be engineered to present topographical signals to cells which, through interactions between the material and active components of the cell membrane, regulate key cellular processes and guide cell fate decisions. However, targeting mechanoresponsive elements that reside within the intracellular domain is a concept that has only recently emerged. Here, we show that mesoporous silicon nanoneedle arrays interact simultaneously with the cell membrane, cytoskeleton, and nucleus of primary human cells, generating distinct responses at each of these cellular compartments. Specifically, nanoneedles inhibit focal adhesion maturation at the membrane, reduce tension in the cytoskeleton, and lead to remodeling of the nuclear envelope at sites of impingement. The combined changes in actin cytoskeleton assembly, expression and segregation of the nuclear lamina, and localization of Yes-associated protein (YAP) correlate differently from what is canonically observed upon stimulation at the cell ...

Nanoneedle-Mediated Stimulation of Cell Mechanotransduction Machinery

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Nanoneedle-Mediated Stimulation of Cell Mechanotransduction Machinery